Ablation of eosinophils with anti‐IL‐5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse

Sasaki, Osamu; Sugaya, Hiroko; Ishida, Kazuhiko; Yoshimura, Kazuya

doi:10.1111/j.1365-3024.1993.tb00619.x

Cited by 111 publications

(56 citation statements)

References 20 publications

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“…This conclusion differs from the results of another study that demonstrated that OVA-pulsed eosinophils are capable of sensitizing mice when injected repeatedly into the peritoneal cavity (12). As eosinophils are associated with helminth parasites at the initial stage of infection (8,10,15,23), it is possible that these cells capture antigens from the helminths, migrate to T-cell-rich regions, and present antigens to T cells to initiate antigen-specific T-cell responses. Therefore, the present study also examined the ability of antigen-exposed eosinophils to prime the naïve T cells.…”

Section: Discussioncontrasting

confidence: 56%

Eosinophils Can Function as Antigen-Presenting Cells To Induce Primary and Secondary Immune Responses toStrongyloides stercoralis

et al. 2006

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Several studies have demonstrated roles for eosinophils during innate and adaptive immune responses to helminth infections. However, evidence that eosinophils are capable of initiating an immune response to parasite antigens is lacking. The goal of the present in vitro study was to investigate the potential of eosinophils to serve as antigen-presenting cells (APC) and initiate an immune response to parasite antigens. Purified eosinophils were exposed to soluble Strongyloides stercoralis antigens, and the expression of various surface markers involved in cell activation was examined. Antigen-exposed eosinophils showed a sixfold increase in expression levels of CD69 and major histocompatibility complex (MHC) class II, a fourfold increase in levels of T-cell costimulatory molecule CD86, and a twofold decrease in levels of CD62L compared to eosinophils cultured in medium containing granulocyte-macrophage colony-stimulating factor. The ability of eosinophils to present antigen to T cells was determined by culturing them with T cells in vitro. Eosinophils pulsed with antigen stimulated antigen-specific primed T cells and CD4 ؉ T cells to increase interleukin-5 (IL-5) production. The blocking of MHC class II expression on eosinophils inhibited their ability to induce IL-5 production by CD4؉ T cells in culture. Antigen-pulsed eosinophils were able to prime naïve T cells and CD4 ؉ T cells in culture and polarized them into Th2 cells producing IL-5 similar to that induced by antigen-loaded dendritic cells. These results demonstrate that eosinophils are capable of activating antigen-specific Th2 cells inducing the release of cytokines and assist in the priming of naïve T cells to initiate Th2 responses against infection. This study highlights the potential of eosinophils to actively induce immune responses against infection by amplifying antigen-specific Th2-cell responses.

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Section: Discussioncontrasting

confidence: 56%

Eosinophils Can Function as Antigen-Presenting Cells To Induce Primary and Secondary Immune Responses toStrongyloides stercoralis

et al. 2006

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“…These findings confirm previous reports in which elimination of IL-5 by mAb treatment (TRFK-5) was shown to abrogate S. stercoralis larval killing in immunized BALB/cByJ mice (18). In contrast, many other groups have found no role for IL-5 in protection from other parasites, however measurable levels of eosinophils could still be found in the peripheral blood, cutaneous tissues, cerebrospinal fluid, liver, and lungs of TRFK-5-treated mice (12,35,(37)(38)(39)(40)(41)(42)(43). Thus, the eosinophils still present in mouse tissues after mAb treatments might still have been able to mediate systemic L3 destruction.…”

Section: Discussionmentioning

confidence: 99%

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Herbert

Lee

et al. 2000

The Journal of Immunology

113

110

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Protective immunity to Strongyloides stercoralis infective larvae in mice has been shown to be dependent on IL-5 based on mAb depletion studies. The goal of this study was to determine the functional role of IL-5 during the innate and adaptive immune response to larval S. stercoralis in mice. In these studies, three strains of mice were used: wild-type C57BL/6J (WT), IL-5 knockout (KO), and IL-5 transgenic (TG). Innate responses to the larvae indicated that there was enhanced survival in the KO animals and decreased survival in the TG animals compared with WT. Furthermore, killing of larvae in TG mice was associated with eosinophil infiltration and degranulation. In studying the adaptive immune response, it was observed that immunization of KO mice did not lead to the development of protective immunity. Experiments were then performed to determine whether KO mice reconstituted with Abs or cells could then develop protective immunity. KO mice displayed protective immunity via a granulocyte-dependent mechanism following injection of purified IgM from immune wild-type animals. Immunity in KO mice could also be reconstituted by the injection of eosinophils at the time of immunization. These eosinophils did not participate in actively killing the challenge infection, but rather were responsible for the induction of a protective Ab response. We conclude that IL-5 is required in the protective immune response for the production of eosinophils, and that eosinophils were involved in larval killing during innate immunity and in the induction of protective Abs in the adaptive immune response.

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“…The function of eosinophils has been studied by modulating their numbers by manipulating interleukin-5 levels (5) (13) or depleting them selectively with a monoclonal antibody against the eotaxin receptor CCR3 (8). Eosinophilia correlates with improved host protection in Angiostrongylus cantonensis (19), Strongyloides ratti (17), Strongyloides stercoralis (12), Onchocerca volvulus (14), and Litomosoides sigmodontis (15) infections. In contrast, the depletion of eosinophils did not alter the course of Schistosoma mansoni (20), Mesocestoides corti (13), and Trichuris muris (3) infections.…”

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confidence: 99%

Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection

et al. 2005

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The attenuation of eosinophilia by the administration of monoclonal antibodies to CCR3 consistently correlates with impairment in worm elimination following primary intraperitoneal Brugia pahangi infections in mice. Host protection was unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic protein 1 (MBP-1), suggesting that eosinophils are essential in host protection but that neither EPO nor MBP-1 alone is.Despite the consistent association of eosinophilia with parasitic infections, evidence supporting a host-protective role in vivo remains elusive (1-4, 16, 22). The function of eosinophils has been studied by modulating their numbers by manipulating interleukin-5 levels (5) (13) or depleting them selectively with a monoclonal antibody against the eotaxin receptor CCR3 (8). Eosinophilia correlates with improved host protection in Angiostrongylus cantonensis (19), Strongyloides ratti (17), Strongyloides stercoralis (12), Onchocerca volvulus (14), and Litomosoides sigmodontis (15) infections. In contrast, the depletion of eosinophils did not alter the course of Schistosoma mansoni (20), Mesocestoides corti (13), and Trichuris muris (3) infections. In the case of filarial parasites, eotaxin and eosinophils have been shown to play a role in host protection (21).The role of eosinophil granule constituents in host protection is also unclear. Purified eosinophil granule proteins have been shown to effectively kill Brugia microfilariae (11), schistosomulae (2), and Trichinella spiralis newborn larvae (10) in vitro. have shown that the death of onchocercal microfilariae following amocarzine treatment was associated with eosinophil degranulation. Electron microscopy analyses showed apposition of eosinophil granule material on the microfilarial surface. However, the requirement of eosinophil granule protein for in vivo host protection has not been studied extensively. In a recent study, EPO Ϫ/Ϫ and wild-type (WT) mice challenged with O. volvulus manifested similar parasite recoveries, suggesting that eosinophil peroxidase (EPO) is not required for host protection in this model (1). In order to investigate the role of the eosinophil granule proteins in host protection, we have now examined the course of Brugia pahangi infection in mice that have undergone targeted mutations in the genes encoding two of the major proteins in the eosinophil granules.C57BL/6 (hereafter WT) mice were obtained from the Jackson Laboratory (Bar Harbor, Maine). EPO Ϫ/Ϫ and MBP-1 Ϫ/Ϫ mice (6, 7) were transferred from the Mayo Clinic, Scottsdale, Arizona, where they were generated and backcrossed with C57BL/6 mice for six generations at the UCHC AAALACaccredited facility. Brugia pahangi third-stage larvae (L3) were provided by one of the following sources: TRS Inc. Monoclonal antibodies against rat RT 6.1 (DS4.23) and 6.2 (6A5) were obtained from Dale Greiner, UMass Medical Center, Worcester, MA. Antibodies were enriched from hybridoma ascites fluid by 50% ammonium sulfate precipitation. The precipitate was dialyzed against phos...

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Ablation of eosinophils with anti‐IL‐5 antibody enhances the survival of intracranial worms of Angiostrongylus cantonensis in the mouse

Cited by 111 publications

References 20 publications

Eosinophils Can Function as Antigen-Presenting Cells To Induce Primary and Secondary Immune Responses toStrongyloides stercoralis

Eosinophils Can Function as Antigen-Presenting Cells To Induce Primary and Secondary Immune Responses toStrongyloides stercoralis

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection

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